There is a need for treatments that protect cells from cell death resulting from episodes of disease, trauma, isolation and removal of tissues or cells from the body, or exposure to toxins. This need extends to treatments for nerve cell loss associated with chronic or acute neurodegenerative disorders or trauma; treatments to minimize tissue damage resulting from ischemia where ischemia may occur as a result of stroke, heart disease, a transplantation event, or other event resulting in a cut-off in nutritional supply to tissues; and treatment to modulate cell death associated with conditions such as osteoporosis or anemia. The absence of an effective cytoprotective therapy can result in either loss of life or a general decline in the quality of life including permanent disability with high health care costs to patients, their families and the health care providers. One approach to minimize pathologic changes has been to attempt to neutralize the oxidative stress that is associated with an accumulation of free radicals in the extracellular space. Mooradian, J. Steroid Biochem. Molec. Biol. 45 (1993) 509-511 has reported that certain estrogens have significant anti-oxidant properties in in vitro biochemical assays but this effect is not seen with all estrogens. Because of the variation in anti-oxidant properties noted by Mooradian in his biochemical assays, he concluded that steroid molecules must have certain anti-oxidant determinants which were as yet unknown. Similar observations concerning steroids with phenolic A rings were reported in WO 95/13076 using biochemical assays to show anti-oxidant activity. The assays used by Mooradian and by WO 95/13076 were biochemical assays and as such did not directly examine the effects on cells of these molecules. U.S. Pat. No. 5,554,601 (1996) however described cell based assays to determine a method of conferring neuroprotection on a population of cells using estrogen compounds based on demonstrated cell protective effects.
Oxidative damage has been associated with a variety of neurodegenerative diseases including Alzheimer's disease (AD); and the aging process. (Benzi et al. Free Radic. Biol. Med. 19, (1995); 77-101, and U.S. Pat. No. 5,554,601 incorporated herein by reference) . Cell death also occurs following an ischemic event in the body resulting from nutrient deprivation which may be associated with oxygen deprivation resulting from an occlusion in a cerebrovascular or cardiovascular location or may be associated with trauma or disease.
There is a need for improved methods of protecting both men and women from the consequences of abnormal cell death in body tissues.